Transdermal local anesthetic patch with injection port

ABSTRACT

Described herein are transdermal delivery devices composed of at least one resealable injection port and at least one local anesthetic reservoir. The device effectively delivers anesthetic to the skin of the subject prior to puncturing the skin by syringes, needle sticks, or other instruments intended to be inserted into the skin. In addition, this device can be used to deliver various therapeutic agents for either locally or systemically.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. provisional application No.61/132,134, filed Jun. 16, 2008 and to U.S. non-provisional applicationSer. No. 12/338,381 filed on Dec. 18, 2008 the contents of the entiretyof which are incorporated by this reference.

BACKGROUND

An overarching fear of needles and needle sticks exists throughout theworld. This fear knows no bounds of age, sex, or race. For many, thisphobia makes visits to the doctor and dentist intolerable and oftentimes a last resort. This ultimately results in missed doctor's anddentist's visits and inadequate healthcare treatment of variousillnesses, diseases and for routine vaccinations.

For people with this phobia coupled with chronic diseases such as, forexample, insulin dependent diabetes, treatment is a daunting task. Thesepatients face the daily task of sticking their finger with a lancet todraw blood to test blood sugar. For a noncompliant patient, thiscomplicates diagnosis and treatment of the condition, and even for themost compliant patient, the task of repeatedly sticking their fingerwith a lancet is extremely painful. In addition, for a compliant patienteach day the patient must administer medication or insulin via aninjection. After administering their medication, proper steriletechniques require one to sterilize the injection site and place abandage where the injection took place. This process is tedious andmundane. Many people fail to follow proper sterile techniques, and as aresult, the injection site may become infected. For those people who dofollow this protocol, the skin is often damaged due to the constantapplication and removal of bandage adhesives. Thus, it would bedesirable for the subject to have a patch containing a local anestheticto numb the injection site, an antiseptic or antimicrobial agent toprevent injection site infection, and either a single use or multi-useinjection port to allow for a pain free injection for as many days asneeded.

SUMMARY

Described herein are transdermal delivery devices composed of at leastone resealable injection port and at least one local anestheticreservoir. The device effectively delivers anesthetic to the skin of thesubject prior to puncturing the skin by syringes, needle sticks, orother instruments intended to be inserted into the skin. In addition,the transdermal delivery device may include a single use patch that doesnot include a local anesthetic refill port. The advantages of theinvention will be set forth in part in the description which follows,and in part will be obvious from the description, or may be learned bypractice of the aspects described below. The advantages described belowwill be realized and attained by means of the elements and combinationsparticularly pointed out in the appended claims. It is to be understoodthat both the foregoing general description and the following detaileddescription are exemplary and explanatory only and are not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate several aspects described below.

FIG. 1 shows the top view of a transdermal delivery device with a singleinjection port, two resealable refill ports, and an anestheticreservoir.

FIG. 2 shows the cross-sectional view of a transdermal delivery devicewith a single injection port, two resealable refill ports, and ananesthetic reservoir.

FIG. 3 shows the top view of a transdermal delivery device with multipleinjection ports, two resealable refill ports, and an anestheticreservoir.

FIG. 4 shows a transdermal delivery device with a replaceable buttonwith and an injection port having multiple adjacent resealable injectionregions.

FIG. 5 shows a transdermal delivery device with multiple resealableinjection ports surrounded by two anesthetic reservoirs without localanesthetic refill ports.

FIG. 6 shows a transdermal delivery device with a single resealableinjection port surrounded by an anesthetic reservoir without a localanesthetic refill port.

FIG. 7 shows the top view of a transdermal delivery device with a singleinjection port, two resealable refill ports, and a compartmentalizedreservoir.

FIG. 8 shows a transdermal delivery device with a replaceable button, aninjection port having multiple adjacent resealable injection regions,and a reservoir surrounding the resealable injection regions.

DETAILED DESCRIPTION

Before the present compounds, compositions, and/or methods are disclosedand described, it is to be understood that the aspects described beloware not limited to specific compositions, compounds, synthetic methods,or uses as such may, of course, vary. It is also to be understood thatthe terminology used herein is for the purpose of describing particularaspects only and is not intended to be limiting.

In this specification and in the claims that follow, reference will bemade to a number of terms that shall be defined to have the followingmeanings:

It must be noted that, as used in the specification and the appendedclaims, the singular forms “a,” “an” and “the” include plural referentsunless the context clearly dictates otherwise. Thus, for example,reference to “a local anesthetic” includes mixtures of two or more suchanesthetics, and the like.

“Optional” or “optionally” means that the subsequently described eventor circumstance can or cannot occur, and that the description includesinstances where the event or circumstance occurs and instances where itdoes not. For example, the phrase “optionally a skin permeabilityenhancer” means that the therapeutic agent may or may not be included.

Effective therapeutic amount refers to the amount of a compound of thepresent invention that offers therapeutic activity after administrationto humans or animals without adverse effects. The therapeutic amount oflocal anesthetic compounds is referred to as concentration of the activecompound and the volume administered.

Described herein are transdermal delivery devices that deliver a localanesthetic to an injection or lancing site. The term “injection site” isthe location on the subject's skin that is going to be punctured by amedical device including but not

The resealable injection port is generally composed of a polymeric,non-allergenic, non-reacting, inert material that permits a medicaldevice such as a syringe or needle to readily pass through the material.During injection, the polymeric material forms a seal around the medicaldevice. Upon removal of the medical device, the polymeric materialsubstantially if not completely closes the hole produced by the medicaldevice. Thus, the resealable injection port can maintain a sterileenvironment during injection and post-injection. The polymeric materialused to make the resealable injection port can be composed of a varietyof different materials such as, for example, silicon, non-allergicrubberized material, or other medically safe synthetic or semi-syntheticplastics. The number of injection ports can vary, as will bedemonstrated below.

The delivery device also contains one or more local anestheticreservoirs for holding the local anesthetic. The local anesthetic isgenerally positioned near the resealable injection port so that the skinat or near the injection site is exposed to the anesthetic and block thenerves of the skin, for a painless entry of a needle or lancet. Thelocal anesthetic can be any topical anesthetic known in the art. In oneaspect, the local anesthetic includes ester based or an amide basedlocal anesthetics or any combination thereof. Examples of amide basedlocal anesthetics include, but are not limited to, articaine, bupicaine,dibucaine, lidocaine, mepivacaine, prilocaine, and ropivacaine. Examplesof ester based local anesthetics include, but are not limited to,benzocaine, chloroprocaine, proparacaine, and tetracaine. In one aspect,the local anesthetic is a combination of both lidocaine and prilocaine.The lidocaine and prilocaine are present at least in a 2:1 ratio byweight, a 1:1 ratio by weight, or any combination thereof. In otheraspects, lidocaine and prilocaine may be present in the amount of 3:1,4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1. Inaddition, any of the local anesthetics mentioned above can be used incombination and are present at least in a 2:1, 3:1, 4:1, 5:1, 6:1, 7:1,8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, or 15:1 ratio by weight. Even upto 2:98, 5:95, 10:90, 25:75, 35:65, 50:50 amount respectively. Theanesthetic can be mixed with carriers such as lipophilic vehicles inorder to enhance the absorption of the anesthetic by the skin. The localanesthetic may be fast-acting or short-acting. For example, one may feela “numbing” sensation within a matter of minutes. However, this numbingsensation may only last a matter of minutes or hours. In another aspect,the local anesthetic may be long acting. In this aspect, one may feel a“numbing” sensation rather quickly (i.e. in a matter of minutes), andthis sensation may last up to at least 18 hours. The selection andamount of the local anesthetic can vary depending upon the size of thedelivery device as well as the number and position of resealableinjection ports present in the device and how long the patch will beused. The shape and size of the transdermal delivery device can varydepending upon the application, which is demonstrated in the figures. Incertain aspects, the shape of the device is a circle, a square, arectangle, an oval, an oblong shape, a triangle, a star, or a squaredepending upon where on the subject the device is applied. In general,the device has an adhesive that permits the attachment of the device tothe skin of the subject. For example, the transdermal delivery devicemay be placed onto a finger (like a band aid), the abdomen, thigh, calf,arm, shoulder, or any other regions of exposed skin on the subject.Adhesives typically used in bandages and the like can be used herein.

The devices described herein can contain one or more optionaltherapeutic agents. The location of the optional therapeutic agents inthe device can vary depending upon the design of the device. In oneaspect, the optional therapeutic agent can be an antiseptic agent, atherapeutic pharmacological, a biologic, a nutriceutical, hormones,antibiotics, nicotine, antifungal agents, antiviral agents, or any painrelieving agent not excluding narcotics. By preventing bacterial, viral,and fungal growth, antiseptic agents maintain sterility either before,during, or post injection. In one aspect, the antiseptic agent can be analcohol including, but not limited to, ethanol, propanol, isopropanol,or any combination thereof; quaternary ammonium compounds including, butnot limited to, benzalkonium chloride, cetyl trimethylammonium bromide,cetylpyridinium chloride, benzethonium chloride, or any combinationthereof; boric acid; chlorhexidine gluconate, hydrogen peroxide, iodine,mercurochrome, ocetnidine dihydrochloride, sodium chloride, sodiumhypochlorite, colloidal silver, silver nitrate, mupirocin, erthromycin,clindamycin, gentamicin, polymyxin, bacitracin, silver, sulfadiazine, orany combination thereof.

In other aspects, the optional therapeutic agent is a vasoconstrictor.Vasoconstriction is the narrowing of blood vessels resulting from thecontraction of the muscular wall of the vessels. When blood vesselsconstrict, the flow of blood is restricted or slowed. Without wishing tobe bound by theory, a vasoconstrictor would increase the time a localanesthetic resided at one location. The vasoconstrictor may preventblood flow washout or dissipation of the local anesthetic. In addition,a vasoconstrictor may limit the amount of bleeding associated with aneedle or lancet stick. Such vasoconstrictors may include phenylephrine,ephedrine sulfate, epinephrine, naphazoline, neosynephrine, vasoxyl,oxymetazoline, or any combination thereof.

In another aspect, the optional therapeutic agent is a skin permeabilityenhancer. The skin is a rigid, almost impermeable layer. Thisimpermeability is attributed to the nature of one very thin top surfacelayer called the stratum corneum. This impermeability creates problemsfor the transdermal delivery of agents which include local anesthetics.Examples of skin permeability enhancers include but are not limited todimethyl sulfoxide (DMSO), lecithin, decyl methyl sulfoxide, dodecyldimethyl phosphine oxide, octyl methyl sulfoxide, nonyl methylsulfoxide, undecyl methyl sulfoxide, lauryl alcohol, diisopropylsebacate, oleyl alcohol, diethyl sebacate, dioctyl sebacate, dioctylazelate, hexyl laurate, ethyl caprate, butyl stearate, dibutyl sebacate,dioctyl adipate, propylene glycol dipelargonate, ethyl laurate, butyllaurate, ethyl myristate, butyl myristate, isopropyl palmitate,isopropyl isostearate, 2-ethylhexyl pelargonate, butyl benzoate, benzylbenzoate, benzyl salicylate, dibutyl phthalate, nicotinates, fattyacids, fatty alcohols, or any combination thereof. In one aspect, theskin permeability enhancer is at least greater than 1% weight pervolume, weight per weight, or mole percent. In another aspect, the skinpermeability enhancer may be at least greater than 1.5%, 2.0%, 2.5%,3.0%, 3.5%, 4.0%, 4.5% up to 50% weight per volume, weight per weight,or mole percent. In one aspect, the skin permeability enhancer isdimethyl sulfoxide. In this aspect, the amount of dimethyl sulfoxide mayrange from 2% to 10%, 2% to 9.5%, 3% to 8%, 3% to 7%, or 4% to 6% weightper volume, weight per weight, by mole percent or any effectivetherapeutic amount relative to the local anesthetic.

In other aspects, anti-inflammatories and anti-dolorosa can be presentin the device to reduce inflammation. This class of drugs functions toblock various inflammatory pathways. For example, non-steroidalanti-inflammatory drugs (NSAIDs) alleviate pain and inflammation bycounteracting cyclooxygenase and preventing the synthesis ofprostaglandins. In one aspect, NSAIDs may be incorporated in thereplaceable button or the semi-permeable reservoir of the transdermaldelivery device. These NSAIDs may include celecoxib, meloxicam,nabumetone, piroxicam, naproxen, oxaprozin, rofecoxib, sulindac,ketoprofen, valdecoxid, anti-tumor necrosis factors, anti-cytokines,anti-inflammatory pain causing bradykinins or any combination thereof.

In another aspect, antihistamines and steroids can be used to preventany allergic reaction or irritation caused by the anesthetic or othertherapeutic agents when the device is used for prolonged periods oftime.

In another aspect, transdermal transport of a local anesthetic and atherapeutic agent can be enhanced by the application of a secondarydriving force either before or after application of the transdermaldelivery device. In certain aspects this secondary driving forceincludes electromotive (electrotransport) force in the form ofiontophoresis, electroosmosis, electroporation, fractional laser; ormechanical force such as magnetic force, vibration, vibroacoustic force,or sonophoretic force such as ultrasound. This force may be applied toenhance the uptake of the local anesthetic into subcutaneous tissue forrapid blocking of pain conduction nerve endings. For example, withoutwishing to be bound by theory, when ultrasound is used, low frequency isused. In one aspect, less than 2.5 MHz is used. In yet another aspect,less than 1 MHz is used. When acoustical vibrations (low frequencyultrasound with vibration—Vibroacoustic) are applied using a specifiedpulse ranging, from one-half second to three seconds, modulated with anoscillatory signal in the frequency range of 1 Hz to 1500 Hz, and havingpulse amplitude in the range of about 20 to 5000 microns, transdermaltransport of a local anesthetic and a therapeutic agent may be furtherenhanced.

FIGS. 1-6 provide numerous designs of the devices described herein.Referring to FIGS. 1 and 2, the transdermal delivery device 10 is apatch having a resealable injection port 11 and a reservoir 12 thatcontains the local anesthetic or any other pharmaceutically acceptablepreparation. On the topside of the device 10, an impermeable substrate13 surrounds the injection port 11 and prevents the local anestheticfrom leaching out of the reservoir. On the underside of the device 10,which is the side that is applied to the surface of the skin, anopposing permeable layer 14 is present and positioned under thereservoir 12. The permeable layer permits the diffusion of the localanesthetic from the reservoir to the skin surface. The permeable layer14 is surrounded by an impermeable material 15, which prevents the localanesthetic from leaching to the sides of the device 10. An adhesive canbe applied to the impermeable material 15, which helps adhere the deviceto the subject's skin. Semipermeable and permeable membranes mayinclude, but are not limited to, materials made from regeneratedcellulose, regenerated cellophane, cellulose ester membranes, chargemosaic membranes, bipolar membranes, amphoteric exchange membranes,anion exchange membranes, dialysis tubing, ethylene-vinyl acetate (EVA)copolymer membranes (e.g. 1-20% vinyl acetate), polyvinylalcohol (PVA)gels, or silicon films.

The device as shown in FIGS. 1 and 2 also permits refilling of thereservoir 12 with local anesthetic or other therapeutic pharmacologicalagents, biologics, and nutriceuticals once the anesthetic hassubstantially or completely diffused from the reservoir. Two resealablerefill ports 16 are present in the device 10. The number and design ofthe ports can vary. For example, with smaller devices, the refill portcan be composed of a polymeric material such as that used in theinjection port, which permits the injection of additional anestheticinto the reservoir without a refill port. The selection of the polymericmaterial will depend upon the volume of the reservoir in the device andif present, the dimensions of the refill port. If larger devices arecontemplated, the refill port can be accessed by a screw top. Thus, thedelivery devices depicted in FIGS. 1-3 can be refilled and reusedmultiple times.

FIG. 2 further depicts inserting a hypodermic needle into the injectionport and injecting a bioactive agent 20 within the dermal or subdermallayers. Within this figure, the contents of the reservoir (i.e. localanesthetic, vasoconstrictor, anti-histamine, etc.) are diffusing 19 intothe epidermis, dermis, and subdermal layers of the skin. The diffusedcontents of the reservoir act on the nerves 18 and blood vessels 17around the transdermal delivery device.

FIG. 3 depicts a variation of the device 10 in FIG. 1. Referring to FIG.3, device 30 has a seven injection ports 31. This device can be used forinjection seven consecutive times. These injections may occur within oneday or over a period of several days. Although not shown, an optionaltether may be placed on the underside of the patch. This tether is athin string made of metal, synthetic plastic, or semi-synthetic plasticwhich may connect the injection ports to one another. This tetherfunctions to support each injection port and to prevent any resealableinjection port from being dislodged or dislocated while removing adevice such as a needle or lancet from the resealable injection port.

FIG. 4 provides another example of a delivery device having multipleinjection ports in a circle so that the injection sites are rotated.Referring to FIG. 4, the device is composed of resealable injection port40, which is shown as attached to the skin 41 of the subject, and areplaceable anesthetic button 42. The resealable injection port 40 asshown in FIG. 4 has eight injection regions, which means that the devicecan be used eight times before discarding the injection port 40. Theinjection port 40 can have an adhesive on the backside so that it can beaffixed to the skin of the subject for extended periods of time. Theresealable injection port 40 has an opening 43 for receiving thereplaceable anesthetic button 42. The top and sides of the button arecomposed of an impermeable material, while the underside of the buttonthat is in contact with the skin is composed of a permeable material.The impermeable and permeable materials described above can be used toproduce the button 42. An adhesive is present on the surface 45 of thebutton, which helps adhere the button to the skin prior to injection.The volume of anesthetic present in the button will vary on thedimension of the button. In general, when the subject is ready toperform an injection, the replaceable anesthetic button is inserted intothe injection port 40 for a sufficient time to numb the desired regionof skin. An injection may be administered to injection region numberone. When the next injection is administered, injection region numbertwo will be used, and this will occur until all eight injection regionsare used. The number of injection regions is not limited in number.After the injection, the replaceable anesthetic button is removed forfuture use. The injection port 40 can remain on the skin of the subjectuntil all of the injection regions have been used.

FIGS. 5 and 6 depict additional devices described herein. As drawn,neither device has a resealable refill port for the local anesthetic;however, these features can easily be added by one of ordinary skill inthe art, if desired. FIG. 5 shows the underside of device 50 (i.e., theside that is applied to the skin). The device 50 is composed of fourresealable injection ports 51. In this aspect, anesthetic reservoirs 52and 53 are adjacent to the injection ports. An adhesive can be appliedto the surfaces 54 and 55, which are composed of an impermeablematerial. Although not shown in FIG. 5, a protective cover can beapplied to the underside of the device 50 (and any of the other devicesdescribed herein) to prevent the anesthetic from leaking as well asdecontamination of the injection port. The protective cover can bereadily peeled off of the device 50 prior to use.

FIG. 6 shows another design of the delivery device. The underside ofdevice 60 as shown in FIG. 6 has a resealable injection port 61surrounded by an anesthetic reservoir 62, where the anesthetic candiffuse from the reservoir to the surface of the skin through apermeable or semipermeable membrane. An adhesive is applied to thesurface 63. The surface 63 and the backside of device 60 are composed ofan impermeable material.

In FIG. 7, the transdermal delivery device 10 is a patch having at leastone resealable injection port 11 and a compartmentalized reservoir 120.The reservoir may be divided by a dividing material 110 and form 1, 2,3, 4, or any number of desired compartmentalized reservoirs 120. Eachcompartmentalized reservoir may contain either a single anesthetic or asingle pharmaceutically acceptable preparation described herein, or thecompartmentalized reservoir may contain a mixture of a local anestheticor any other pharmaceutically acceptable preparation described herein.For example, within FIG. 7, the grid-like dashes within onecompartmentalized reservoir 120 indicates the presence of a separateanesthetic, pharmaceutically acceptable preparation, biologic, ornutriceutical when compared with the other compartmentalized reservoir120 having only vertical dashes. These pharmaceutically acceptablepreparations, biologics, or nutriceuticals include but are not limitedto local anesthetic agents, different therapeutic agents, differentvasoconstrictors, different antiseptic agents, different antimicrobialagents, different antifungal agents, different antiviral agents,different skin permeability enhancers, different anti-inflammatoryagents, or any combination thereof. On the topside of the device 10, animpermeable substrate 13 surrounds the injection port 11 and preventsthe local anesthetic from leaching out of the reservoir. On theunderside of the device 10, which is the side that is applied to thesurface of the skin, an opposing permeable layer 14 is present andpositioned under the reservoir 120. The permeable layer permits thediffusion of the local anesthetic from the reservoir to the skinsurface. The permeable layer 14 is surrounded by an impermeable material15, which prevents the local anesthetic from leaching to the sides ofthe device 10. An adhesive can be applied to the impermeable material15, which helps adhere the device to the subject's skin. Semipermeableand permeable membranes may include, but are not limited to, materialsmade from regenerated cellulose, regenerated cellophane, cellulose estermembranes, charge mosaic membranes, bipolar membranes, amphotericexchange membranes, anion exchange membranes, dialysis tubing,ethylene-vinyl acetate (EVA) copolymer membranes (e.g. 1-20% vinylacetate), polyvinylalcohol (PVA) gels, or silicon films.

The device as shown in FIG. 7 also permits refilling of the reservoir120 with local anesthetic or other therapeutic pharmacological agents,biologics, and nutriceuticals once the anesthetic, the therapeuticpharmacological agents, the biologics, and/or nutriceuticals havesubstantially or completely diffused from the compartmentalizedreservoir. Resealable refill ports 16 may be present in the device 10.If present, the number of refill ports 16 may vary. In addition, thenumber of injection ports 11 may vary also. For example, with smallerdevices, the refill port can be composed of a polymeric material such asthat used in the injection port, which permits the injection ofadditional anesthetic or pharmaceutically acceptable preparation intothe reservoir without a refill port. Thus, if desired, the deliverydevice depicted in FIG. 7 can be modified for multi-use or single usepurposes further described herein.

FIG. 8 provides another example of a delivery device having multipleinjection ports in a circle so that the injection sites are rotated.Referring to FIG. 8, the device is composed of resealable injection port40, which is shown as attached to the skin 41 of the subject, and areplaceable anesthetic button 42. The resealable injection port 40 asshown in FIG. 8 has eight injection regions, which means that the devicecan be used eight times before discarding the injection port 40. Theinjection port 40 can have an adhesive on the backside so that it can beaffixed to the skin of the subject for extended periods of time. Theresealable injection port 40 has an opening 43 for receiving thereplaceable anesthetic button 42. The top and sides of the button arecomposed of an impermeable material, while the underside of the buttonthat is in contact with the skin is composed of a permeable material.The impermeable and permeable materials described above can be used toproduce the button 42. An adhesive is present on the surface 45 of thebutton, which helps adhere the button to the skin prior to injection.The volume of anesthetic present in the button will vary on thedimension of the button. In general, when the subject is ready toperform an injection, the replaceable anesthetic button is inserted intothe injection port 40 for a sufficient time to numb the desired regionof skin. An injection may be administered to injection region numberone. When the next injection is administered, injection region numbertwo will be used, and this will occur until all eight injection regionsare used. The number of injection regions is not limited in number.After the injection, the replaceable anesthetic button is removed forfuture use. The injection port 40 can remain on the skin of the subjectuntil all of the injection regions have been used. Also, acompartmentalized reservoir 410 may surround the injection ports. Thisreservoir may be a single reservoir or divided into two, three, four, orany number of desired compartments. Each compartmentalized reservoir maycontain either a single anesthetic or pharmaceutically acceptablepreparation described herein, or the each compartmentalized reservoirmay contain a mixture of a local anesthetic or any otherpharmaceutically acceptable preparation described herein such ashormones, nicotine, vitamins, narcotics, nutriceuticals,anti-Alzheimer's medication, Parkinson's medication, autism medication,and various other medications used to treat neurological diseases,anti-tumor necrosis factors, anti-tumor agents, heart medications, orvarious other transdermally transportable therapeutic agents describedherein or known to one of ordinary skill in the art the for preventionand treatment of local and systemic diseases.

The optional therapeutic agents described above can be incorporated in anumber of different locations within the delivery device. For example,an antiseptic agent can be applied to the surface of the injection port(topside and/or underside) to kill any bacteria, virus, or fungus thatmay be present on the syringe and maintain a sterile environment at theinjection site. Alternatively, in order to maintain a sterileenvironment at the injection port, the injection port can be coveredwith an antiseptic cap or cover. In other aspects, one or moretherapeutic agents can be mixed with the anesthetic and the mixtureintroduced into the anesthetic reservoir. In this aspect, thetherapeutic agent diffuses to the skin with the anesthetic.

The devices described herein can be applied to the skin of a subjectwhere the skin is ultimately going to be punctured in order to reduce oreliminate pain associated with the puncture. The underside of theinjection port(s) has non irritating adhesive which will facilitatesticking to the skin when applied. Such adhesive may include a topicalsilicone adhesive, a water based adhesive, epoxies, urethanes,methacrylates, polyacrylates, rubber-based adhesives, polysiloxaneadhesives, pressure sensitives, starches, and phenolics of varying tacklevels depending on the patient's skin and the task at hand. Theadhesive material may be an acrylic adhesive including at least onepolymer selected from homopolymers of acrylic esters, copolymers of twoor more types of acrylic ester units and copolymers of acrylic estersand other functional monomers. Acrylic esters include, but are notlimited to, butyl(meth)acrylate, pentyl(meth)acrylate,hexyl(meth)acrylate, heptyl(meth)acrylate, octy(meth)acrylate,nonyl(meth)acrylate, decyl(meth)acrylate. Functional monomers include,but are not limited to, monomers containing a hydroxyl group, such ashydroxyethyl(meth)acrylate, hydroxypropyl (meth)acrylate, monomerscontaining a carboxyl group such as carboxyl methacrylate and monomerscontaining an amide group such as methacrylamide,dimethylmethacrylamide, etc.

Specific examples of acrylate monomers, which are suitable for use withthe present invention include, but are not limited to methacrylic acid,butyl acrylate, butyl methacrylate, hexyl acrylate, hexyl methacrylate,2-ethylbutyl acrylate, 2-ethylbutyl methacrylate, isooctyl acrylate,isooctyl methacrylate, 2-ethylhexyl acrylate, dodecylmethacrylate,tridecyl acrylate, tridecyl methacrylate, and mixtures thereof.

Specific examples of functional monomers which are copolymerizable withthe above-recited alkyl acrylates or methacrylates, which can also beused include, but are not limited to acrylic acid, methacrylic acid,maleic acid, maleic anhydride, hydroxyethyl acrylate, hydroxypropylacrylate, acrylamide, dimethylacrylamide, acrylonitrile,dimethylaminoethyl acrylate, dimethylaminoethyl methacrylate,tert-butylaminoethyl acrylate, tert-butylaminoethyl methacrylate,methoxyethyl acrylate, and mixtures thereof.

Specific examples of suitable rubber-based pressure sensitive adhesivesinclude but are not limited to hydrocarbon polymers, such as natural andsynthetic polyisoprenes, polybutylenes, polyisobutylene (PIB),styrene/butadiene polymers, styrene-isoprene-styrene block copolymers,hydrocarbon polymers such as butyl rubber, halogen-containing polymerssuch as polyacrylic nitrile, polytetrafluoroethylene, polyvinylchloride, polyvinylidene chloride, and polychlorodiene, andpolysiloxane, and other copolymers thereof.

Specific examples of polysiloxanes include but are not limited tosilicone pressure sensitive adhesives, which are based on two majorcomponents: a polymer, or gum, and a tackifying resin. The polysiloxaneadhesive may be prepared by cross-linking the gum, typically a highmolecular weight polydiorganosiloxane with the resin to produce athree-dimensional silicate structure via a condensation reaction in anappropriate organic solvent. Various aspects of formulating polysiloxaneadhesives are known in the art. Suitable silicone pressure-sensitiveadhesives are commercially available and include the silicone adhesivessold as BIO-PSA®, Dow Corning Corporation, Medical Products, Midland,Mich.

As described above, the local anesthetic diffuses from the anestheticreservoir onto the skin. The local anesthetic numbs a portion of theskin at or near the injection site. The duration of contact between theskin and the anesthetic can vary depending upon the type of puncture orinjection that is made. In one aspect, the device is applied 30 to 60minutes in advance to allow the local anesthetic to enter the dermalnever fibers in the skin and block them so that when the injectionoccurs, the subject does not feel pain. The devices described hereinhave numerous applications including, but not limited to, reducing oreliminating pain associated with the injection of bioactive agents suchas drugs and both pediatric and adult vaccines; the drawing of bloodfrom a subject; the use of permanent infusion ports; the use ofartery-venous (A-V) shunts used in kidney dialysis; the use of ports toinject various steroids and other therapeutic agents into the diseasedor damaged tissue such as muscles, tendons, and joints; their use bypodiatrists for corns; their use as a band aid to draw the blooddroplets to test for glucose levels in diabetics and other bloodchemistry analysis; and the insertion of canulas for intravenousinfusion, catheters, PICC lines for long IV infusions, Swan Ganzcatheter intersection, nerve blocks to relive pain, and injections ofpainful joints.

The devices described herein are particularly useful in the treatment ofchronic disorders, systemic diseases, and hormone replacement therapy.Such chronic and systemic diseases include, for example, diabetes,psoriasis, and eczema. In the case of diabetes, the subject iscontinuously monitoring blood sugar levels as well as self-administeringinsulin. The continuous pricking and injections can be traumatic to thesubject over time. The devices described herein alleviate the pain andstress associated with this, which will ultimately ensure that thesubject is diligent with monitoring their blood sugar levels andconsistently administering their medication.

In another aspect, the transdermal delivery device can be used forreducing or eliminating pain associated with bruises, cuts, poison ivyirritation, insect bites and stings, localized skin diseases, andallergic reactions without using the injection port.

In yet another aspect, the transdermal delivery device can be used todeliver either locally or systemically any one of the substances,chemicals, hormones, or therapeutic agents mentioned above.

Numerous modifications and alternative arrangements may be devised bythose skilled in the art without departing from the spirit and scope ofthe present invention and the appended claims are intended to cover suchmodifications and arrangements. Thus, while the present invention hasbeen described above with particularity and detail in connection withwhat is presently deemed to be the most practical and preferredembodiments of the invention, it will be apparent to those of ordinaryskill in the art that numerous modifications, including, but not limitedto, variations in size, materials, shape, form, function and manner ofoperation, assembly and use may be made without departing from theprinciples and concepts set forth herein.

1. A transdermal delivery device comprising at least one re-sealableinjection port and at least one local anesthetic reservoir fordelivering the anesthetic to the skin of a subject.
 2. The transdermaldelivery device of claim 1, wherein the device comprises a patchcomprising (a) a replaceable button, wherein the replaceable buttoncomprises a local anesthetic reservoir; and (b) an injection port forreceiving the replaceable button.
 3. The transdermal delivery device ofclaim 1, wherein the device further comprises at least one re-sealablerefill port for refilling the local anesthetic reservoir.
 4. Thetransdermal delivery device of claim 1, wherein the device comprises afirst side and second side, wherein the first side comprises animpermeable material surrounding the injection port, the second sidecomprises a permeable or semi-permeable material, wherein theimpermeable material of the first side and the permeable orsemi-permeable material of the second side forms the local anestheticreservoir, and the permeable or semi-permeable material permits thediffusion of the local anesthetic from the local anesthetic reservoir.5. The transdermal delivery device of claim 4, wherein the periphery ofthe permeable or semi-permeable material on the second side issurrounded by a second impermeable material.
 6. The transdermal deliverydevice of claim 5, wherein an adhesive is present on the surface of thesecond impermeable material.
 7. The transdermal delivery device of claim4, wherein one or more re-sealable refill ports are present on the firstside of the device.
 8. The transdermal delivery device of claim 4,wherein the device comprises two or more injection ports.
 9. Thetransdermal delivery device of claim 1, wherein the local anestheticcomprises an ester based local anesthetic, an amide based localanesthetic, or a combination thereof.
 10. The transdermal deliverydevice of claim 9, wherein the amide based local anesthetic comprisesarticaine, bupivacaine, dibucaine, lidocaine, mepivacaine, prilocaine,ropivacaine, or any combination thereof.
 11. The transdermal deliverydevice of claim 9, wherein the amide based local anesthetic compriseslidocaine, prilocaine, or a combination thereof.
 12. The transdermaldelivery device of claim 11, wherein when lidocaine and prilocaine arepresent, they are present in at least a ratio of 2:1 by weight.
 13. Thetransdermal delivery device of claim 9, wherein the ester based localanesthetic comprises benzocaine, chloroprocaine, proparacaine,tetracaine, or any combination thereof.
 14. The transdermal deliverydevice of claim 1, wherein an antiseptic agent is coated on at least onesurface of the at least one re-sealable injection port.
 15. Thetransdermal delivery device of claim 1, wherein an antiseptic agent iscoated on both surfaces of the at least one re-sealable injection port.16. The transdermal delivery device of claim 14, wherein the antisepticagent, antimicrobial agent, antifungal agent, or antiviral agentcomprises an alcohol, a quaternary ammonium compounds comprisingbenzalkonium chloride, cetyl trimethylammonium bromide, boric acid,chlorhexidine gluconate, hydrogen peroxide, iodine, mercurochrome,octenidine dihydrochloride, sodium chloride, sodium hypochlorite, silvernitrate, or any combination thereof.
 17. The transdermal delivery deviceof claim 1, wherein the further comprising one or more therapeuticagents admixed with the local anesthetic.
 18. The transdermal deliverydevice of claim 1, wherein the therapeutic agent comprises avasoconstrictor, a skin permeability enhancer, an anti-inflammatoryagent, an antihistamine, or any combination thereof.
 19. The transdermaldelivery device of claim 18, wherein the vasoconstrictor comprisesphenylephrine, ephedrine sulfate, epinephrine, naphazoline,neosynephrine, vasoxyl, oxymetazoline, or any combination thereof. 20.The transdermal delivery device of claim 18, wherein the skinpermeability enhancer comprises dimethyl sulfoxide, lecithin, decylmethyl sulfoxide, dodecyl dimethyl phosphine oxide, octyl methylsulfoxide, nonyl methyl sulfoxide, undecyl methyl sulfoxide, laurylalcohol, diisopropyl sebacate, oleyl alcohol, diethyl sebacate, dioctylsebacate, dioctyl azelate, hexyl laurate, ethyl caprate, butyl stearate,dibutyl sebacate, dioctyl adipate, propylene glycol dipelargonate, ethyllaurate, butyl laurate, ethyl myristate, butyl myristate, isopropylpalmitate, isopropyl isostearate, 2-ethyl-hexyl pelargonate, butylbenzoate, benzyl benzoate, benzyl salicylate, dibutyl phthalate, or anycombination thereof.
 21. The transdermal delivery device of claim 18,wherein the anti-inflammatory agent comprises celecoxib, meloxicam,nabumetone, piroxicam, naproxen, oxaprozin, rofecoxib, sulindac,ketoprofen, valdecoxib, or any combination thereof.
 22. The transdermaldelivery device of claim 1, further comprising a short actinganesthetic, a long acting anesthetic, or any combination thereof havinga predetermined volume.
 23. A method for reducing or eliminating painassociated with a syringe, needle stick, or lancet stick comprising (a)applying the transdermal delivery device of claim 1 on the surface ofthe skin of a subject for a sufficient time to numb the skin, and (b)inserting the syringe, needle stick, or lancet stick in the resealableinjection port.
 24. A method for reducing or eliminating pain comprisingapplying the transdermal delivery device of claim 1 to the skin whereinthe skin is bruised, cut, irritated by poison ivy, insect stings, bitesor localized skin diseases, or affected by allergic reactions withoutusing the injection port.
 25. The transdermal delivery device of claim1, wherein the local anesthetic reservoir is compartmentalized into atleast two separate reservoirs.
 26. The transdermal delivery device ofclaim 25, wherein the at least two separate reservoirs comprisedifferent local anesthetic agents, different therapeutic agents,different vasoconstrictors, different antiseptic agents, differentantimicrobial agents, different antifungal agents, different antiviralagents, different skin permeability enhancers, differentanti-inflammatory agents, or any combination thereof.